Neuroblastoma (NB) is the most common extra-cranial solid tumor in children below 5 years of age. Despite aggressive regimen, survival rate of high-risk NB patients is only ~40%. The majority of deaths occur due to treatment resistance and disease relapse. Cellular immunotherapy, such as chimeric antigen receptor (CAR)-T cells, offers a less toxic and potentially durable cure for patients with NB. However, CAR-T cells have mediated anti-tumor responses in only a subset of pediatric patients. Inhibitory immune cells residing within neuroblastoma tumor mass in cancer patients decrease the success of immunotherapy. Given the high cost of these therapies and heterogenous response, there is an ur...

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Neuroblastoma (NB) is the most common extra-cranial solid tumor in children below 5 years of age. Despite aggressive regimen, survival rate of high-risk NB patients is only ~40%. The majority of deaths occur due to treatment resistance and disease relapse. Cellular immunotherapy, such as chimeric antigen receptor (CAR)-T cells, offers a less toxic and potentially durable cure for patients with NB. However, CAR-T cells have mediated anti-tumor responses in only a subset of pediatric patients. Inhibitory immune cells residing within neuroblastoma tumor mass in cancer patients decrease the success of immunotherapy. Given the high cost of these therapies and heterogenous response, there is an urgent and unmet clinical need to develop methods that enable prediction of treatment outcomes, thereby enabling the selection of patients that would benefit from these treatments. Current methods to evaluate these inhibitory immune cells are invasive and/or inaccurate. In this project, we will advance a novel and clinically translatable quantitative imaging-based methodology, termed "nano-radiomics" to non-invasively profile the immune "make-up" of solid tumors. Successful completion of proposed work will provide necessary pre-clinical data to pursue testing of nano-radiomics in CAR-T clinical trials for neuroblastoma and other pediatric solid tumors, providing the potential for immediate impact during immunotherapies for children with cancer. When translated into the clinic, nano-radiomics would enable pre-treatment patient stratification by detecting the presence of inhibitory immune cells that exhibit CAR-T resistance. Furthermore, it would guide interventions for converting resistant tumors into CAR-T responsive tumors.

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